Gold nanoparticles have a multitude of valuable applications as catalysts, in semiconductors, in the rapidly emerging fields of nanoscience and nanotechnology, medical imaging, biomedicine, therapeutics and others. Powerful surface plasmon absorption of gold, for example, makes gold nanoparticles useful in applications such as biosensors. They are environmentally and biologically benign. Other example gold nanoparticle applications include smart windows, rewritable electronic paper, electronic panel displays, memory components, and others.
Many traditional methods for the production of gold nanoparticles require use of potentially harmful chemicals such as hydrazine, sodium borohydride and dimethyl formamide (“DMF”) in lengthy synthetic processes. These chemicals pose handling, storage, and transportation risks that add substantial cost and difficulty to gold nanoparticle production. These harmful chemicals also make it impractical, if not impossible, to produce gold nanoparticles in-vivo. Some production methods include the application of sodium borohydride to reduce a gold salt to produce gold nanoparticles. This production method is unsuitable in the presence of target specific peptides because sodium borohydride will reduce chemical functionalities present on peptide backbones, thus either reducing or eliminating the biospecificity of biomolecules. Still another disadvantage of many methods for producing gold nanoparticles relates to the heat required for their production. This adds further costs and complications to production of gold nanoparticles.
Still other problems in the art relate to production of gold nanoparticle chains and arrays. Many applications benefit from the use of nanochains verses nanoparticles. In some imaging applications, for example, individual nanoparticles may not be detectable. A nanochain or nanoarray, on the other hand, is more easily detected. In the prior art predictable and consistent methods for producing gold nanochains and arrays are not known.
Still other problems relate to the relatively instability of nanoparticles. Gold nanoparticles tend to quickly agglomerate and/or to oxidize. Known stabilization methods include storage in citrate. Citrates can be strongly acidic, making their handling and use difficult. Also, transfer of the gold nanoparticle from the stabilizing citrate is also difficult. For materials such as nitrates, glucoses, starches, and nitrogen-based materials, for example, transfer of gold nanoparticles from a citrate stabilizer is very difficult or even impossible. The sodium borohydride reduction method typically uses thiols to stabilize gold nanoparticles. Gold nanoparticles stabilized by thiols cannot be readily exchanged onto peptides or other biomolecules because of the strong interaction of gold metal with thiol groups.
Still other problems are related to obtaining a desired size of gold nanoparticles. Currently known production methods do not allow for well defined size distribution of gold nanoparticles.
Other problems in the art relate to radioactive gold nanoparticles. Radioactive gold nanoparticles are useful, for example, in nanomedicine applications. Gold nanoparticles are potentially useful for treatment of disease as they can deliver agents directly into cancerous cells and cellular components (e.g., a tumor site) with a higher concentration of radioactivity (higher dose of radioactivity). Each gold nanoparticle contains several atoms of gold, which are typically radioactive Au-198/199. Radioactive gold nanoparticles can also be easily tagged with oligonucleotides and peptides that are selective for receptors over expressed by diseased tissue.
These unique advantages present promising opportunities in the design and development of tumor specific nanotherapeutic agents for the treatment of cancer. Unfortunately, traditional production methods for gold nanoparticles have proven to be problematic when using radioactive gold. By way of example, traditional methods that utilize NaBH4 (or other reducing agents) for the production of gold nanoparticles at macroscopic levels often fail when used at tracer levels to produce nanoparticulate radioactive Au-198/199.